Clinical variability of target volume description in conformal radiotherapy planning

PURPOSE: The pivotal step in radiation planning is delineation of the target volume and production of a treatment plan to encompass this. This study assesses the variation of physicians in creation of these volumes. METHODS AND MATERIALS: Three radiologists and eight radiation oncologists outlined the gross tumour volume (GTV) on the planning CT scans of four cases with T3 bladder cancer. In addition, the radiation oncologists (RO) created a planning target volume according to a set protocol for all cases. Volumes were produced and comparison of these volumes and the position of the isocenters were analysed. In addition, the margins allowed were measured and compared. RESULTS: There was a maximum variation ratio (largest to smallest volume outlined) of the GTV in the four cases of 1.74 among radiologists and 3.74 among oncologists. There was a significant difference (p = 0.01) in mean GTV between RO and the radiologists. The mean GTV of the RO exceeded the radiologists by a factor of 1.29 with a mean difference of 13.4 cm3. The variation ratio in PTV among oncologists ranged from 1.25 to 3.33. There was no significant difference in mean PTV values between the two groups of ROs divided by specialization in uro-oncology. The mean variation in location of the isocenter from the centroid of the radiologists' volume in the four cases was from 2.6 to 5.7 mm. There was, however, a wide range of values from 1.4 mm to 24.1 mm. Median margin per case ranged from 14.7 to 18.7 mm. Minimum margins allowed in each case varied from minus 7 mm to 9 mm. CONCLUSION: This study demonstrates significant interphysician variability in producing target volumes and radiation plans for conformal radiotherapy. The scale of this difference is clearly of significance, with up to 3-fold variation in volumes delineated by clinicians. The factors leading to these differences will be further addressed. The existence of such variability, however, clearly needs to be accepted as a factor in the overall uncertainty analysis in conformal radiotherapy planning.     

Predictors of improved outcome for patients with localized prostate cancer treated with neoadjuvant androgen ablation therapy and three-dimensional conformal radiotherapy

PURPOSE: To identify prognostic variables that predict for improved biochemical and local control outcome in patients with localized prostatic cancer treated with neoadjuvant androgen deprivation (NAAD) and three-dimensional conformal radiotherapy (3D-CRT). MATERIALS AND METHODS: Between 1989 and 1995, 213 patients with localized prostate cancer were treated with a 3-month course of NAAD that consisted of leuprolide acetate and flutamide before 3D-CRT. The purpose of NAAD in these patients was to reduce the preradiotherapy target volume so as to decrease the dose delivered to adjacent normal tissues and thereby minimize the risk of morbidity from high-dose radiotherapy. The median pretreatment prostate-specific antigen (PSA) level was 15.3 ng/mL (range, 1 to 560 ng/mL). The median 3D-CRT dose was 75.6 Gy (range, 64.8 to 81 Gy), and the median follow-up time was 3 years (range, 1 to 7 years). RESULTS: The significant predictors for improved outcome as identified in a multivariate analysis included pretreatment PSA level < or = 10.0 ng/mL(P < .00), NAAD-induced preradiotherapy PSA nadir < or = 0.5 ng/mL (P < .001), and clinical stage < or = T2c (P < .04). The 5-year PSA relapse-free survival rates were 93%, 60%, and 40% for patients with pretreatment PSA levels < or = 10 ng/mL, 10 to 20 ng/mL, and greater than 20 ng/mL, respectively (P < .001). Patients with preradiotherapy nadir levels < or = 0.5 ng/mL after 3 months of NAAD experienced a 5-year PSA relapse-free survival rate of 74%, as compared with 40% for patients with higher nadir levels (P < .001). The incidence of a positive biopsy among 34 patients pretreated with androgen ablation was 12%, as compared with 39% for 117 patients treated with 3D-CRT alone who underwent a biopsy (P < .001). CONCLUSION: For patients treated with NAAD and high-dose 3D-CRT, pretreatment PSA, preradiotherapy PSA nadir response, and clinical stage are important predictors of biochemical outcome. Patients with NAAD-induced PSA nadir levels greater than 0.5 ng/mL before radiotherapy are more likely to develop biochemical failure and may benefit from more aggressive therapies.     

bcl-2/bax ratio as a predictive marker for therapeutic response to radiotherapy in patients with prostate cancer

This study examines in detail the HLA associations of 74 patients (40 women and 34 men) with bullous pemphigoid (BP) and compares their immunogenetic profile with that of 604 unrelated control subjects (238 women and 366 men). Correlations were sought between HLA antigens and the various BP disease parameters investigated. The presence of milia was the only clinical or laboratory finding which was linked with a specific HLA antigen, HLA-DQ6, in both men and women with BP (P < 0.01). BP has previously been linked with the HLA-DQ7 antigen and this association was confirmed in 39 of our patients (14 women and 25 men). Twelve of these patients (four women and eight men) were homozygous for HLA-DQ7. The association of HLA-DQ7 with BP was gender-restricted and only significant for men (P < 0.01). No equivalent HLA disease susceptibility risk factor could be identified for our female BP patients. This difference in HLA association between men and women with BP has not been reported previously, and its significance for disease pathogenesis is not known. No specific link could be found between HLA-DQ7 and BP for any of the clinical, immunofluorescence, western blotting, treatment or prognostic disease factors studied.     

Initial clinical experience with computer-controlled conformal radiotherapy of the prostate using a 50-MeV medical microtron

PURPOSE: We have described previously a model for delivering computer-controlled radiation treatments. We report here on the implementation and first year's clinical experience with such treatments using a 50 MeV medical microtron. METHODS AND MATERIALS: The microtron is equipped with a multileaf collimator and is capable of setting up and treating a sequence of fixed fields called segments, under computer control. An external computer derives machine parameters for the segments from a three-dimensional treatment planning system, transfers them to the microtron control computer, checks the machine settings before allowing dose delivery to begin, and records the treatment. We describe the patient treatment methodology, portal film acquisition, electronic portal imaging, and quality assurance. RESULTS: Patient treatments began in July 1992, comprising six-segment conformal treatments of the prostate. Using the recorded treatment data, the system performance has been examined and compared to other treatment machines. The average treatment time is 10 min, of which 4 min is for computer-controlled setup and irradiation; the remaining time is for patient positioning and checking of clearances. Long-term reproducibility of computer-controlled setup of the gantry and multileaf position is better than 0.5 degrees and 1 mm, respectively. Termination due to a machine fault has occurred in 5.5% of treatments, improving to 2.5% in recent months. CONCLUSION: Our initial experience indicates that computer-controlled segmental therapy can be performed reliably on a routine basis. Treatment times with the microtron are significantly shorter than with conventional linacs, and setup accuracy is consistent with that needed for conformal therapy. We believe that treatment times can be further improved through software upgrades and integration of electronic portal imaging.     

A prostate gland volume of more than 75 cm3 predicts for a favorable outcome after radical prostatectomy for localized prostate cancer

OBJECTIVE: This study aimed to describe the morphology of cystic disorders of the corneal epithelium by confocal microscopy. DESIGN: The study design was a prospective evaluation of confocal microscopic images of patients with cystic corneal disorders. PARTICIPANTS: Thirteen patients (19 eyes) were included. The corneal disorders included four patients with corneal decompensation (Fuchs' dystrophy), five patients with epithelial basement membrane dystrophy (e.g., Cogan's microcystic and map-dot dystrophies), one patient with Meesmann's dystrophy, and three patients with recurrent erosion syndrome of unknown etiology. Confocal images of diseased corneas were compared with those of ten normal control eyes (ten subjects). INTERVENTION: All patients were examined by slit-lamp biomicroscopic analysis and confocal microscopic analysis (Tomey, Erlangen-Temmenlohe, Germany). Image analysis was used to identify the corneal epithelial structures correlated with the corresponding pathology. MAIN OUTCOMES MEASURES: Confocal microscopy was used to assess the size, shape, light scatter, and reflection of the cysts. RESULTS: Slit-lamp examination results showed corneal epithelial cystic lesions in all cases. Confocal microscopy was able to identify cystic lesions in 9 (69.2%) of 13 patients. Of the four patients in whom lesions could not be found by confocal microscopy, three had recurrent erosion syndrome and the other one had epithelial basement membrane dystrophy. The confocal images were compatible with the clinical and histologic pictures of the disease. Normal control eyes did not show any epithelial lesion, either by biomicroscopy or confocal microscopy. CONCLUSIONS: Confocal microscopy provides an in vivo evaluation of cystic epithelial corneal lesions. This study shows that confocal microscopy is suitable for examining cystic lesions of the corneal epithelium. Nevertheless, it is not as sensitive as biomicroscopy in detecting cystic lesions in certain corneal conditions.     

High dose combination radiotherapy for the treatment of localized prostate cancer

PURPOSE: We evaluate the efficacy of high dose combination radiotherapy for the treatment of localized prostate cancer. MATERIALS AND METHODS: A total of 212 patients with localized prostate cancer (T1-T3) were treated with transperineal radioactive seed implantation followed by 45 Gy. external beam radiation therapy. Patients with Gleason scores of 2-5 were treated with 125iodine at a minimum peripheral dose of 120 Gy., while 103palladium at a minimum peripheral dose of 90 Gy. was used for those with Gleason scores of 7-10. Patients with Gleason 6 diploid tumors were treated with 125iodine and those with aneuploid tumors were treated with 103palladium. Biochemical failure was defined as inability to achieve a prostate specific antigen nadir value of 0.5 ng./ml. or less. No patient was treated with androgen deprivation therapy. RESULTS: The 212 patients have a minimum of 24 months of followup (mean 33 months). Prostate specific antigen 0.5 ng./ml. or less was reached by 72% of the patients (152 of 212) and positive biopsies were detected in 13.9% (20 of 144). Using life table survivorship analysis the probability of initial biochemical success at 5 years was 91% (95% confidence interval, 83 to 97). The probability of subsequent failure following an initial success was 11% (95% confidence interval, 6 to 20) at 24 months. The complications of combination therapy included proctitis in 21.4% (47 of 212 men), impotence in 38% (38 of 100), urinary retention in 1.5%, incontinence in 2.8%, rectoprostate fistula in 2.4%, rectal wall breakdown in 0.5% and urethral stricture in 0.5%. Six patients (2.8%) required colostomy and urinary diversion. CONCLUSIONS: Short-term responses to high dose combination radiotherapy for localized prostate cancer are promising. The morbidity is acceptable. Further long-term followup is warranted to assess this treatment.     

The role of PSA in the radiotherapy of prostate cancer

Pretreatment prostate-specific antigen (PSA) level is the single most important prognostic factor for patients undergoing radiotherapy for clinically localized prostate cancer. When combined with Gleason score and T-stage, pretreatment PSA enhances our ability to accurately predict pathologic stage. Patients with pretreatment PSA levels > 10 ng/mL are at high risk for biochemical failure when treated with conventional radiation alone. A PSA nadir of > 1 ng/mL and a post-treatment PSA > 1.5 ng/mL are associated with a high risk of biochemical failure. Postoperative radiotherapy delivered while the tumor burden is low (eg, PSA < 1 ng/mL) predicts a favorable outcome. Many of these conclusions about the usefulness of pretreatment PSA are based on the assumption that PSA can be used as a surrogate end point for disease-free and overall survival from prostate cancer. However, this assumption still remains to be validated by phase III trials.     

Inverse radiotherapy planning for a concave-convex PTV in cervical and upper mediastinal regions. Simulation of radiotherapy using an Alderson-RANDO phantom. Planning target volume

It is a common practice in healthcare to provide comfort and relief from distressing symptoms with the use of intravenous fluids when the patient is no longer able to ingest an adequate amount of fluid. If hydration is not provided to a patient, the medical professional is thought to be negligent of the patient's needs, to consign the patient to a horrible death, and even to shorten the patient's life. On the contrary, dehydration in terminal illness has not been found to produce distressing symptoms or to shorten life span; it may even be beneficial.     

Multiple transrectal ultrasound-guided biopsies for the detection of prostate cancer and determination of tumor volume, grade, and seminal vesicle invasion

Of 60 cases of neurotoxicity related to occupational exposures of workers at plants producing acrylamide monomers, cases involving neurotoxicity related to jobs using polymers with acrylamide monomer contamination have not been widely reported. In 1992, two patients were referred to the Division of Occupational and Environmental Health, Department of Family and Community Health, Marshall University School of Medicine, in Huntington, West Virginia for evaluation. The patients had worked in different coal preparation plants in southern West Virginia for over 10 years and had exposure to an acrylamide polymer flocculent contaminated with acrylamide monomer. Both patients had no instruction on proper use of, or the dangers of, acrylamide and were not given adequate safety equipment. Patient A developed Parkinsonism and Patient B peripheral neuropathies with a neurogenic bladder. These two case reports highlight the need to reemphasize the basic tenets of occupational health and safety. Many chemicals are being introduced into mining operations and awareness of potential toxic exposures and new diseases not previously reported in the mining industry must become part of the surveillance system by mine management and labor safety committees. Further studies on the extent of acrylamide neurotoxicity in the mining industry is encouraged.     

Comparison of laparoscopic and minilaparotomy pelvic lymphadenectomy for prostate cancer staging in a community practice

OBJECTIVES: To compare the cost-effectiveness and morbidity of minilaparotomy (MINILAP) and laparoscopic pelvic lymphadenectomy (LAP) in a community practice setting. METHODS: We reviewed our experience with 44 consecutive patients with prostate cancer who had staging pelvic lymphadenectomy from January 1992 through April 1995 in a general health maintenance organization urology practice. Of this group, 22 men had LAP and 22 men had MINILAP. RESULTS: MINILAP and LAP groups were similar in age (mean 67 years). Gleason score (mean 7.2 and 6.8), prostate-specific antigen level (mean 46 and 49 ng/mL), and clinical stage (T1 to T3). Operative time was statistically significantly shorter for MINILAP (mean 1.2 hours) than for LAP (mean 2.9 hours). Complication rate was 9.1% for MINILAP and 31.8% for LAP. Lymph node metastasis was found in 45% of MINILAP patients and in 27% of LAP patients. Mean initial hospital stay was 1.0 day for MINILAP and 1.6 days for LAP. Total hospital stay including hospital readmission for complications was 1.5 days for MINILAP and 2.6 days for LAP. Cost of MINILAP was at least $1900 less than that of LAP because of shorter total hospital stay, shorter operation time, and lower equipment cost. CONCLUSIONS: Compared with LAP, MINILAP was more cost-effective and produced less morbidity. Patient satisfaction with the procedures was similar. MINILAP is an excellent alternative to LAP for prostate cancer staging in general urology practice.     

Comparison of radical prostatectomy and iodine 125 interstitial radiotherapy for the treatment of clinically localized prostate cancer: a 7-year biochemical (PSA) progression analysis

OBJECTIVES: To evaluate the relative efficacy of brachytherapy to radical prostatectomy, we compared biochemical progression rates from a published series of men who underwent iodine 125 (125I) interstitial radiotherapy for localized prostate cancer to a similar group of men who underwent anatomic radical prostatectomy using appropriate end points. METHODS: Seventy-six men who underwent anatomic radical prostatectomy between 1988 and 1990 were carefully matched for Gleason score and clinical stage to a recently reported contemporary series of patients treated at another institution with 125I brachytherapy without adjuvant treatment. The definition of biochemical progression was a serum PSA level greater than 0.2 ng/mL after anatomic radical prostatectomy and greater than 0.5 ng/mL for brachytherapy-treated patients. RESULTS: The 7-year actuarial PSA progression-free survival following anatomic radical prostatectomy was 97.8% (95% confidence interval [CI], 85.6% to 99.7%) for this group of men selected to match the brachytherapy group, compared to 79% (95% CI not published) for men treated with 125I interstitial radiotherapy. CONCLUSIONS: Using comparative end points for biochemical-free progression, failure rates may be higher following 125I interstitial radiotherapy compared to anatomic radical prostatectomy. These data provide a better comparison of biochemical progression than previously published studies and emphasize the need for caution in interpreting the relative efficacy of brachytherapy in controlling localized prostate cancer.     

三维适形放疗配合腔内后装治疗宫颈癌的临床研究

Objective: The aim of our study was to evaluate the outcome and complications of cervical cancer patients undergoing conventional intracavitary brachytherapy (ICBT) treated with 3D-conformal radiotherapy (3DCRT). Methods: Sixty cervical cancer patients were divided randomly into the conformal group and the conventional group. Thirty patients treated with 3D-conformal radiotherapy in the 3DCRT group, when the whole pelvic received DT 40 Gy, a planning CT scan of each patient was obtained and the second 3DCRT therapy plan was taken. Then, continued to irradiate to 50 Gy. At last, 3DCRT was boosted at local involved volumes to the total close of 60 Gy. When 3DCRT was combined with intracavitary brachytherapy, the dose of brachytherapy to point A was 30 Gy/5 fractions. In the conventional group, after a total tumor dose of 40 Gy was delivered by the whole pelvic irradiation, the four-field technique was used to irradiate the total pelvic and regional nodes (median close of 10 Gy), and the involved volumes were boosted to 60 Gy and the dose of brachytherapy to point A was 30 Gy-36 Gy/5-6 fractions. Moreover, both groups were combined with intracavitary brachytherapy respectively. Results: The 1, 2, 3-year survival rates for the 3DCRT group and the conventional group were 96.7%, 93.3%, 90.0% and 86.6%, 76.7%,70% respectively (P = 0.04, P = 0.02 and P = 0.02). There was a statistically significant difference between the two groups.Compared to the two groups each other in toxic effects, except for the Ⅰ-Ⅱ grade rectal and bladder reaction and pelvic fibrosis which was lower in the 3DCRT group (P = 0. 007, P = 0. 006 and P = 0. 015), the side effects were similar and well tolerated in two groups. Conclusion: The all-course 3DCRT combined with intracavitary brachytherapy can be considered as an effective and feasible approach to cervical cancer and may significantly improve the survival rate and reduce the late toxicity. This new rote for 3DCRT merits need further evaluation with large patient numbers and longer follows up.     

A software tool for the quantitative evaluation of 3D dose calculation algorithms

Current methods for evaluating modern radiation therapy treatment planning (RTP) systems include the manual superposition of calculated and measured isodose curves and the comparison of a limited number of calculated and measured point doses. Both techniques have significant limitations in providing quantitative evaluations of the large number of dose data generated by modern RTP systems. More sophisticated comparison techniques have been presented in the literature, including dose-difference and distance-to-agreement (DTA) analyses. A software tool has been developed that uses superimposed isodose plots, dose-difference, and DTA distributions to quantify errors in computed dose distributions. Dose-difference and DTA analyses are overly sensitive in regions of high- and low-dose gradient, respectively. The logical union of locations that fail both dose-difference and DTA acceptance criteria, termed the composite evaluation, is calculated and displayed. The composite evaluation provides a method for the physicist to efficiently identify regions that fail both the dose-difference and DTA acceptance criteria. The tool provides a computer platform for the quantitative comparison of calculated and measured dose distributions.     

Comparison of subcapsular and total orchiectomy for treatment of metastatic prostate cancer

OBJECTIVES: To determine whether subcapsular orchiectomy provides suboptimal treatment of metastatic prostate cancer when used to avoid the psychologic consequences of the empty scrotum that results from total orchiectomy. METHODS: We compared testosterone and prostate-specific antigen levels and survival of 37 patients who underwent total orchiectomy and 37 patients who underwent subcapsular orchiectomy for metastatic prostate cancer. RESULTS: The two groups of 37 patients were similar by clinical parameters. Postoperatively, testosterone levels were 21 +/- 11 ng/dL for subcapsular versus 21 +/- 9 ng/dL for total orchiectomy patients. Tumor response was similar in the two groups when assessed by prostate-specific antigen measured 3 weeks, 6 months, and 1, 2, and 3 years postoperatively. Survival was similar when assessed using Kaplan-Meier analysis (P = 0.76). CONCLUSIONS: Subcapsular orchiectomy is a viable option for treatment of metastatic prostate cancer.     

Comparison of D2 and D3 dopamine receptor affinity of dopaminergic compounds in rat brain

This study used quantitative autoradiography to simultaneously evaluate the relative affinities of dopaminergic compounds for dopamine D2 and D3 receptors in rat brain. PD 152255, PD 128907, and l-nafadotride exhibited significantly higher affinity for cerebellar dopamine D3 sites than [3H]quinpirole-labeled sites in caudate/putamen (6.3-, 6.0-, and 2.3-fold, respectively). In contrast, chlorpromazine, risperidone, and domperidone were more potent at striatal dopamine D2 receptors (3.8-, 31-, and 40-fold, respectively). Dopamine, quinelorane, (+)-UH 232, and RS-trans-7-OH-PIPAT exhibited relatively little D2/D3 selectivity.     

Intracellular levels of SGP-2 (Clusterin) correlate with tumor grade in prostate cancer

Our previous observations in LNCaP cells in vitro demonstrated an association between apoptotic cell death resistance and SGP-2 (Clusterin) overexpression. Accordingly, we hypothesized that high levels of cellular SGP-2 would aid in identifying biologically aggressive prostate cancer cells with unique survival advantages. To test this hypothesis, 40 archival radical prostatectomy and/or biopsy specimens of varying grades of prostate cancer were subjected to immunohistochemical SGP-2 staining. The resulting epithelial stains were quantified subjectively on a scale of 1-3 by four independent observers. Benign prostatic epithelial cells from young donors served as controls and showed a consistently weak staining intensity. In contrast, prostate cancer specimens showed varying degrees of staining intensity that correlated with a Gleason pattern (P = 0.006). This correlation supports the hypothesis that protection from apoptotic death may account, in part, for biologically aggressive tumor behavior.     

Traffic to lymph nodes of PC-3 prostate tumor cells in nude mice visualized using the luciferase gene as a tumor cell marker

Tumor cell traffic between intramuscular tumors experimentally induced in nude mice and lymph nodes was studied using PC-3.luc prostate adenocarcinoma cells permanently transfected with the luciferase gene as a tumor cell marker. This sensitive approach allowed the detection of 1 luminescent tumor cell mixed with 1 x 10(7) unlabeled PC-3 cells and of 1 tumor cell/lymph node. PC-3.luc cells inoculated in nude mice showed a 1000-fold expansion, accompanied by a 4.5-fold increase in tumor cell density (tumor cell number/gram of tumor), during the first 90 days of primary tumor growth. No macroscopic secondary tumors were found in organs, other than lymph nodes, by the end of the experiment. Tumor cell spread to lymph nodes was detected at Day 21, when there were 2 x 10(5) tumor cells at the inoculation sites, before discrete primary tumors could be identified. The total tumor cell burden in the tested lymph nodes was modeled by a power function of primary tumor cell number (determination coefficient R2 = 0.9472). By the end of the experiment, on Day 110, there were 1.8 metastatic cells in the studied lymph nodes for every 1000 primary tumor cells. These results suggest that empirically obtained tumor-specific indexes could be used to characterize the invasion of lymph nodes by tumor cells. The path of spread for PC-3.luc cells from intramuscular sites appears to follow the lymphatic system, and at no time during the experiment were tumor cells found in blood. An upper limit of no more than 16 blood-circulating tumor cells was established for these experiments. The observation of tumor cells that were invading the lymphatic system from the onset of tumor growth but unable to establish secondary tumors in other organs emphasizes the potential of this procedure in studying the multi-step nature of metastasis.     

One core positive prostate biopsy is a poor predictor of cancer volume in the radical prostatectomy specimen

PURPOSE: In view of the recent increase in patients presenting with only 1 core positive for prostate carcinoma, we examined the correlation in tumor volume between the biopsy and the subsequent radical prostatectomy specimen. MATERIALS AND METHODS: We studied a total of 169 consecutive prostate biopsies with matched radical prostatectomy specimens and selected 48 patients with only 1 positive core. RESULTS: Cancers found in the biopsy regardless of their size were associated with a wide range of cancer volume in the radical prostatectomy specimens, and the amount of cancer in the biopsy was a poor predictor of the volume of cancer in the prostatectomy specimen. Even with a cancer of 3 mm. or less in the biopsy, 57% of patients had cancer of clinically significant volume (greater than 0.5 ml.). Other modalities for the evaluation of prostate cancer such as Gleason score and clinical stage were not helpful in segregating patients with clinically significant from those with insignificant volume of cancer. However, when combined with a preoperative serum prostate-specific antigen higher than 10 ng./ml., 1 core positive biopsy could reliably predict the presence of cancer of significant volume. CONCLUSIONS: One core only positive prostate biopsy, when accompanied by an elevated serum prostate specific antigen value (greater than 10 ng./ml.), strongly suggests the presence of clinically significant cancer.     

Combined orchiectomy and external radiotherapy versus radiotherapy alone for nonmetastatic prostate cancer with or without pelvic lymph node involvement: a prospective randomized study

PURPOSE: We compare the combination of orchiectomy and radiotherapy to radiotherapy alone as treatment for pelvic confined prostate cancer, that is T1-4, pN0-3, M0 (TNM classification). MATERIALS AND METHODS: In this prospective study 91 patients with clinically localized prostate cancer were, after surgical lymph node staging, randomized to receive definitive external beam radiotherapy (46) or combined orchiectomy and radiotherapy (45). Patients treated with radiotherapy alone had androgen ablation at clinical disease progression. The effects on progression-free, disease specific and overall survival rates were calculated. RESULTS: After a median followup of 9.3 years (range 6.0 to 11.4) clinical progression was seen in 61% of the radiotherapy only patients (group 1) and in 31% of the combined treatment patients (group 2) (p = 0.005). The mortality was 61 and 38% (p = 0.02), and cause specific mortality was 44 and 27%, respectively (p = 0.06), in groups 1 and 2. The differences in favor of combined treatment were mainly caused by lymph node positive tumors. For node negative tumors there was no significant difference in survival rates. CONCLUSIONS: The progression-free, disease specific and overall survival rates for patients with prostate cancer and pelvic lymph node involvement are significantly better after combined androgen ablation and radiotherapy than after radiotherapy alone. These results strongly suggest that early androgen deprivation is better than deferred endocrine treatment for these patients.